Variation in the mu-opioid receptor gene (OPRM1) moderates the influence of maternal sensitivity on child attachment.

The endogenous opioid system is thought to play an important role in mother-infant attachment. In infant rhesus macaques, variation in the µ-opioid receptor gene (OPRM1) is related to differences in attachment behavior that emerges following repeated separation from the mother; specifically, infants carrying at least one copy of the minor G allele of the OPRM1 C77G polymorphism show heightened and more persistent separation distress, as well as a pattern of increased contact-seeking behavior directed towards the mother during reunions (at the expense of affiliation with other group members). Research in adult humans has also linked the minor G allele of the analogous OPRM1 A118G polymorphism with greater interpersonal sensitivity. Adopting an interactionist approach, we examined whether OPRM1 A118G genotype and maternal (in)sensitivity are associated with child attachment style, predicting that children carrying the G allele may be more likely to develop an ambivalent attachment pattern in response to less sensitive maternal care. The sample consisted of 191 mothers participating with their children (n = 223) in the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) project, a community-based, birth cohort study of Canadian mothers and their children assessed longitudinally across the child's development. Maternal sensitivity was coded from at-home mother-child interactions videotaped when the child was 18 months of age. Child attachment was assessed at 36 months using the Strange Situation paradigm. As predicted, G allele carriers, but not AA homozygotes, showed increasing odds of being classified as ambivalently attached with decreasing levels of maternal sensitivity. Paralleling earlier non-human animal research, this work provides support for the theory that endogenous opioids contribute to the expression of attachment behaviors in humans.

Diagnostic value of abdominal follow-up sonography in polytrauma patients: A retrospective study.

In many German trauma centres, it is routine to perform abdominal follow-up sonography (AFS) 6 h after admission for patients with multiple trauma, even if the clinical course is uneventful and multi-slice computed tomography (MSCT) reveals no abdominal pathology. However, this approach is not recommended in the German Guidelines for trauma, and recent studies have questioned the value of AFS to these patients. The present study aimed to evaluate the revised German Guidelines for trauma with respect to the omission of AFS.We included patients with multiple injuries with no clinical signs of abdominal trauma and with normal abdominal MSCT. We collected clinical data of 370 consecutive patients who underwent AFS (Group A) and another 370 consecutive patients who did not undergo AFS (Group B).No abdominal injury was missed by the omission of AFS, and thus, no patient suffered from its omission or benefitted from the use of AFS. In our study population, the negative predictive value of normal MSCT results combined with no clinical signs of abdominal trauma was 100% (95% confidence interval: 99.5%-100.0%).This single-centre study conducted in a large German trauma centre demonstrates AFS to have no utility in the diagnosis of abdominal injury. Moreover, omission of AFS for conscious patients without clinical signs of abdominal trauma and with negative abdominal MSCT does not appear to have negative consequences in terms of missed abdominal injury.Therefore, AFS can be safely omitted in the majority of cases of polytrauma, which simplifies the imaging workup tremendously.

Multiple Sclerosis Performance Test: validation of self-administered neuroperformance modules.

BACKGROUND AND PURPOSE: The purpose was to determine the test-retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self-administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression-based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example. METHODS: Substudy 1 assessed test-retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples. RESULTS: The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician-administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample. CONCLUSIONS: The self-administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting.

Identification of charged amino acids required for nuclear localization of human L1 ORF1 protein.

BACKGROUND: Long Interspersed Element 1 (LINE-1) is a retrotransposon that is present in 500,000 copies in the human genome. Along with Alu and SVA elements, these three retrotransposons account for more than a third of the human genome sequence. These mobile elements are able to copy themselves within the genome via an RNA intermediate, a process that can promote genome instability. LINE-1 encodes two proteins, ORF1p and ORF2p. Association of ORF1p, ORF2p and a full-length L1 mRNA in a ribonucleoprotein (RNP) particle, L1 RNP, is required for L1 retrotransposition. Previous studies have suggested that fusion of a tag to L1 proteins can interfere with L1 retrotransposition. RESULTS: Using antibodies detecting untagged human ORF1p, western blot analysis and manipulation of ORF1 sequence and length, we have identified a set of charged amino acids in the C-terminal region of ORF1p that are important in determining its subcellular localization. Mutation of 7 non-identical lysine residues is sufficient to make the resulting ORF1p to be predominantly cytoplasmic, demonstrating intrinsic redundancy of this requirement. These residues are also necessary for ORF1p to retain its association with KPNA2 nuclear pore protein. We demonstrate that this interaction is significantly reduced by RNase treatment. Using co-IP, we have also determined that human ORF1p associates with all members of the KPNA subfamily. CONCLUSIONS: The prediction of NLS sequences suggested that specific sequences within ORF1p could be responsible for its subcellular localization by interacting with nuclear binding proteins. We have found that multiple charged amino acids in the C-terminus of ORF1p are involved in ORF1 subcellular localization and interaction with KPNA2 nuclear pore protein. Our data demonstrate that different amino acids can be mutated to have the same phenotypic effect on ORF1p subcellular localization, demonstrating that the net number of charged residues or protein structure, rather than their specific location, is important for the ORF1p nuclear localization. We also identified that human ORF1p interacts with all members of the KPNA family of proteins and that multiple KPNA family genes are expressed in human cell lines.

Pleiotropy of the Drosophila melanogaster foraging gene on larval feeding-related traits.

Little is known about the molecular underpinning of behavioral pleiotropy. The Drosophila melanogaster foraging gene is highly pleiotropic, affecting many independent larval and adult phenotypes. Included in foraging's multiple phenotypes are larval foraging path length, triglyceride levels, and food intake. foraging has a complex structure with four promoters and 21 transcripts that encode nine protein isoforms of a cGMP dependent protein kinase (PKG). We examined if foraging's complex molecular structure underlies the behavioral pleiotropy associated with this gene. Using a promotor analysis strategy, we cloned DNA fragments upstream of each of foraging's transcription start sites and generated four separate forpr-Gal4s. Supporting our hypothesis of modular function, they had discrete, restricted expression patterns throughout the larva. In the CNS, forpr1-Gal4 and forpr4-Gal4 were expressed in neurons while forpr2-Gal4 and forpr3-Gal4 were expressed in glia cells. In the gastric system, forpr1-Gal4 and forpr3-Gal4 were expressed in enteroendocrine cells of the midgut while forpr2-Gal4 was expressed in the stem cells of the midgut. forpr3-Gal4 was expressed in the midgut enterocytes, and midgut and hindgut visceral muscle. forpr4-Gal4's gastric system expression was restricted to the hindgut. We also found promoter specific expression in the larval fat body, salivary glands, and body muscle. The modularity of foraging's molecular structure was also apparent in the phenotypic rescues. We rescued larval path length, triglyceride levels (bordered on significance), and food intake of for0 null larvae using different forpr-Gal4s to drive UAS-forcDNA. In a foraging null genetic background, forpr1-Gal4 was the only promoter driven Gal4 to rescue larval path length, forpr3-Gal4 altered triglyceride levels, and forpr4-Gal4 rescued food intake. Our results refine the spatial expression responsible for foraging's associated phenotypes, as well as the sub-regions of the locus responsible for their expression. foraging's pleiotropy arises at least in part from the individual contributions of its four promoters.

Surface induced vibrational modes in the fluorescence spectra of PTCDA adsorbed on the KCl(100) and NaCl(100) surfaces.

We report a combined experiment-theory study on low energy vibrational modes in fluorescence spectra of perylene-3,4,9,10-tetracarboxylic acid dianhydride (PTCDA) molecules. Using very low coverages, isolated molecules were adsorbed on terrace sites or at sites located at residual steps on (100) oriented alkali halide films (KCl and NaCl). The low energy modes couple to the optical transition only because the PTCDA molecule is geometrically distorted (C2v) upon adsorption on the surface; they would be absent for the parent planar (D2h) PTCDA molecule. The modes differ in number and energy for molecules adsorbed on regular terrace sites and molecules adsorbed at step edge sites. Modes appearing for step edge sites have the character of frustrated rotations. Their coupling to the optical transition is a consequence of the further reduced symmetry of the step edge sites. We find a larger number of vibrational modes on NaCl than on KCl. We explain this by the stronger electrostatic bonding of the PTCDA on NaCl compared to KCl. It causes the optical transition to induce stronger changes in the molecular coordinates, thus leading to larger Franck-Condon factors and thus stronger coupling. Our results demonstrate how optical spectroscopy can be used to gain information on adsorption sites of molecules at low surface concentrations.

Polygenic associations of neurodevelopmental genes in suicide attempt.

The risk for suicidal behavior (SB) is elevated in schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD), but also occurs in subjects without psychiatric diagnoses. Genome-wide association studies (GWAS) on SB may help to understand this risk, but have been hampered by low power due to limited sample sizes, weakly ascertained SB or a reliance on single-nucleotide protein (SNP)-by-SNP analyses. Here, we tried to mitigate such issues with polygenic risk score (PRS) association tests combined with hypothesis-driven strategies using a family-based sample of 660 trios with a well-ascertained suicide attempt (SA) outcome in the offspring (Genetic Investigation of Suicide and SA, GISS). Two complementary sources of PRS information were used. First, a PRS that was discovered and validated in the GISS SA revealed the polygenic association of SNPs in 750 neurodevelopmental genes, which was driven by the SA phenotype, rather than the major psychiatric diagnoses. Second, a PRS based on three different genome-wide association studies (on SCZ, BPD or MDD) from the Psychiatric Genomics Consortium (PGC) showed an association of the PGC-SCZ PRS in the SA subjects with and without major psychiatric diagnoses. We characterized the PGC-SCZ overlap in the SA subjects without diagnoses. The extended major histocompatibility complex region did not contribute to the overlap, but we delineated the genic overlap to neurodevelopmental genes that partially overlapped with those identified by the GISS PRS. Among the 590 SA polygenes implicated here, there were several developmentally important functions (cell adhesion/migration, small GTPase and receptor tyrosine kinase signaling), and 16 of the SA polygenes have previously been studied in SB (BDNF, CDH10, CDH12, CDH13, CDH9, CREB1, DLK1, DLK2, EFEMP1, FOXN3, IL2, LSAMP, NCAM1, nerve growth factor (NGF), NTRK2 and TBC1D1). These novel genome-wide insights, supported by two lines of evidence, suggested the importance of a polygenic neurodevelopmental etiology in SB, even in the absence of major psychiatric diagnoses.

Adolescent spinal pain: The pediatric orthopedist's point of view.

INTRODUCTION: Ten to twenty percent of persons experience spinal pain during growth. Causes are diverse in adolescents, and it is essential to determine etiology rapidly so as to guide optimal management. HYPOTHESIS: It is important for the pediatric orthopedist to understand the natural history of conditions inducing spinal pain. MATERIAL AND METHODS: A retrospective study included 116 adolescents presenting with spinal pain at the Hôpital Nord (Marseille, France) between January 1, 2009 and January 1, 2014. Malignant tumoral etiologies were excluded. Mean patient age was 13.6 years. Risser ranged between >0 and <5. Interview and clinical examination (skin, spine, neurologic examination, general clinical examination) were systematic; depending on results, complementary examinations (imaging, biology, biopsy) were prescribed. RESULTS: There were 32 cases of non-specific adolescent low back pain, 31 of lumbar or thoracolumbar scoliosis, 23 of spinal growth dystrophy (Scheuermann's disease), 13 of isthmic lysis, 5 of spondylolisthesis, 8 of transitional lumbosacral hinge abnormality, 2 of discal hernia, 1 of osteoid osteoma and 1 of eosinophil granuloma. Treatment was often non-operative when diagnosis was sufficiently early. In case of failure, surgery could generally be considered. DISCUSSION: Correctly indicated non-operative management or surgery changes the natural history of these pathologies. The aim of treatment is to resolve pain in adolescence, as it risks becoming chronic and disabling by adulthood.

Maternal childhood adversity and child temperament: an association moderated by child 5-HTTLPR genotype.

We examined transgenerational effects of maternal childhood adversity on child temperament and a functional promoter polymorphism, 5-HTTLPR, in the serotonin-transporter gene (SLC6A4) as potential moderators of such maternal influences in 154 mother-child dyads, recruited into a longitudinal birth cohort study. We examined the interactive effects of maternal childhood experience using an integrated measure derived from Childhood Trauma Questionnaire (CTQ) and Parental Bonding Index (PBI). Triallelic genotyping of 5-HTTLPR was performed. A measure of 'negative emotionality/behavioural dysregulation' was derived from the Early Childhood Behaviour Questionnaire at 18 and 36 months. Negative emotionality/behavioural dysregulation was highly stable between 18 and 36 months and predicted psychosocial problems at 60 months. After controlling multiple demographics as well as both previous and concurrent maternal depression there was a significant interaction effect of maternal childhood adversity and offspring 5-HTTLPR genotype on child negative emotionality/behavioural dysregulation (ß = 1.03, t(11,115) = 2.71, P < .01). The results suggest a transgenerational effect of maternal developmental history on emotional function in the offspring, describing a pathway that likely contributes to the familial transmission of vulnerability for psychopathology.

An overview of the neurobiology of suicidal behaviors as one meta-system.

Suicidal behaviors (SB) may be regarded as the outmost consequence of mental illnesses, or as a distinct entity per se. Regardless, the consequences of SB are very large to both society and affected individuals. The path leading to SB is clearly a complex one involving interactions between the subject's biology and environmental influences throughout life. With the aim to generate a representative and diversified overview of the different neurobiological components hypothesized or shown implicated across the entire SB field up to date by any approach, we selected and compiled a list of 212 gene symbols from the literature. An increasing number of novel gene (products) have been introduced as candidates, with half being implicated in SB in only the last 4 years. These candidates represent different neuro systems and functions and might therefore be regarded as competing or redundant explanations. We then adopted a unifying approach by treating them all as parts of the same meta-system, using bioinformatic tools. We present a network of all components connected by physical protein-protein interactions (the SB interactome). We proceeded by exploring the differences between the highly connected core (~30% of the candidate genes) and its peripheral parts, observing more functional homogeneity at the core, with multiple signal transduction pathways and actin-interacting proteins connecting a subset of receptors in nerve cell compartments as well as development/morphology phenotypes and the stress-sensitive synaptic plasticity processes of long term potentiation/depression. We suggest that SB neurobiology might also be viewed as one meta-system and perhaps be explained as intrinsic unbalances acting within the core or as imbalances arising between core and specific peripheral components.

Genetic variation in oxytocin rs2740210 and early adversity associated with postpartum depression and breastfeeding duration.

Mothers vary in duration of breastfeeding. These individual differences are related to a variety of demographic and individual maternal factors including maternal hormones, mood and early experiences. However, little is known about the role of genetic factors. We studied single-nucleotide polymorphisms (SNPs) in the OXT peptide gene (rs2740210; rs4813627) and the OXT receptor gene (OXTR rs237885) in two samples of mothers from the Maternal adversity, Vulnerability and Neurodevelopment study (MAVAN), a multicenter (Hamilton and Montreal, Canada) study following mothers and their children from pregnancy until 7 years of age. Data from the Hamilton site was the primary sample (n = 201) and data from Montreal was the replication sample (n = 151). Breastfeeding duration, maternal mood (measured by the CES-D scale) and early life adversity (measured by the CTQ scale) were established during 12 months postpartum. In our primary sample, polymorphisms in OXT rs2740210, but not the other SNPs, interacted with early life adversity to predict variation in breastfeeding duration (overall F8,125 = 2.361, P = 0.021; interaction effect b = -8.12, t = -2.3, P = 0.023) and depression (overall F8,118 = 5.751, P ≤ 0.001; interaction effect b = 6.06, t = 3.13, P = 0.002). A moderated mediation model showed that higher levels of depression mediated the inverse relation of high levels of early life adversity to breastfeeding duration, but only in women possessing the CC genotype [effect a' = -3.3401, 95% confidence interval (CI) = -7.9466 to -0.0015] of the OXT SNP and not in women with the AA/AC genotype (a' = -1.2942, ns). The latter findings (moderated mediation model) were replicated in our Montreal sample (a' = -0.277, 95% CI = -0.7987 to -0.0348 for CC; a' = -0.1820, ns for AA/AC).

Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: associations and gene-environment interactions with childhood/adolescent physical assault.

The complex etiology of suicidal behavior has frequently been investigated in relation to monoaminergic neurotransmission, but other neurosystems have shown alterations as well, involving excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA) molecular components, together with the modulating polyamines. Sufficiently powered and family-based association studies of glutamatergic and GABAergic genes with suicidal behavior are nonexistent, but several studies have been reported for polyamines. We therefore conducted, for the first time ever, an extensive family-based study of 113 candidate single-nucleotide polymorphisms (SNPs) located in 24 glutamatergic and GABA genes, in addition to interrelated polyaminergic genes, on the outcome of severe suicide attempts (SAs). The family-based analysis (n=660 trios) was supplemented with gene-environment interaction (G × E), case-control (n=519 controls) and subgroup analyses. The main observations were the previously unreported association and linkage of SNPs rs2268115 and rs220557 in GRIN2B, as well as of SNPs rs1049500 and rs2302614 in ODC1 (P<10(-2)). Furthermore, GRIN2B haplotypic associations were observed, in particular with a four-SNP AGGC haplotype (rs1805247-rs1806201-rs1805482-rs2268115; P<10(-5)), and a third SNP rs7559979 in ODC1 showed G × E with serious childhood/adolescent physical assault (P<10(-4)). SA subjects were characterized by transdiagnostic trait anger and past year alcohol-drug use disorders, but not by alcohol-drug use at SA, depression, anxiety or psychosis diagnoses. We also discuss a first ever confirmatory observation of SNP rs6526342 (polyaminergic SAT1) in SA, originally identified in completed suicides. The results suggest that specific genetic variants in a subset of glutamatergic (GRIN2B) and polyaminergic (ODC1) neurosystem genes may be of importance in certain suicidal subjects.

Family-based study of HTR2A in suicide attempts: observed gene, gene × environment and parent-of-origin associations.

While suicidal behavior is frequently accompanied by serotonergic system alterations, specific associations with genetic variation in the serotonin 2A receptor (HTR2A) gene have been inconsistent. Using a family-based study design of 660 offspring who have made a suicide attempt (SA) and both parents, we conducted an association and linkage analysis using single-nucleotide polymorphisms (SNPs) with extensive gene coverage, and included the study of parent-of-origin (POE) and gene-environment interaction (G × E), also using previously unstudied exposures. The main finding was a G × E between the exon 1 SNP rs6313 and exposure to cumulative types of lifetime stressful life events (SLEs), driven by overtransmission of CT and undertransmission of TT, both in relation to other genotypes. Further exploratory analysis revealed a significant POE in this G × E in female subjects, which followed a polar overdominant inheritance pattern. In addition, rs6310 and rs6305 were found to significantly associate with SA in the total sample. A G × E in female subjects (rs7322347 × physical assault in childhood/adolescence) confirmed features of a previously observed association with SA. Other potentially interesting nominally significant findings were observed, but like the G × E of rs7322347 did not pass a false-discovery rate cutoff. Taken together, this study found multiple associations of HTR2A SNPs on SA, with strongest statistical evidence for a G × E involving rs6313, and further suggested the importance of taking into account different inheritance patterns and G × Es with regard to HTR2A.

Immunophysiology of Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus (Mitchill), and the relationship to parasitic copepod, Dichelesthium oblongum (Abilgaard) infection.

The copepod parasite, Dichelesthium oblongum, is known to infect the Atlantic sturgeon, Acipenser oxyrinchus oxyrinchus, within the area near New York city, USA, known as the NY Bight. The gross pathology associated with the juvenile and adult copepod stages along with the parasite's link in causing changes in sturgeon osmoregulatory capabilities has led us to investigate the host immunophysiology in relation to this host-parasite system. All the host variables, which included gill Na(+) -K(+) -ATPase activity, serum alkaline phosphatase (AP) and white blood cell differential counts, were affected in a non-linear manner by the copepod parasite. The parasites increased the host gill Na(+) -K(+) -ATPase activity and serum AP along with the percentage granulocytes while decreasing the percentage lymphocytes. A new method, developed to sample and preserve white blood cells in the field for future flow cytometry analysis, proved adequate. The effects of fish size, location and time of sampling were accounted for by the use of generalized linear models, and their effects on the host variables are discussed.

Dopamine receptors D1 and D2 are related to observed maternal behavior.

The dopamine pathway and especially the dopamine receptors 1 and 2 (DRD1 and DRD2) are implicated in the regulation of mothering in rats. Evidence for this in humans is lacking. Here, we show that genetic variation in both DRD1 and DRD2 genes in a sample of 187 Caucasian mothers predicts variation in distinct maternal behaviors during a 30-min mother-infant interaction at 6 months postpartum. Two DRD1 single-nucleotide polymorphisms (SNPs rs265981 and rs686) significantly associated with maternal orienting away from the infant (P = 0.002 and P = 0.003, respectively), as did DRD1 haplotypes (P = 0.03). Two DRD2 SNPs (rs1799732 and rs6277) significantly associated with maternal infant-directed vocalizing (P = 0.001 and P = 0.04, respectively), as did DRD2 haplotypes (P = 0.01). We present evidence for heterosis in DRD1 where heterozygote mothers orient away from their infants significantly less than either homozygote group. Our findings provide important evidence that genetic variation in receptors critical for mothering in non-human species also affect human maternal behaviors. The findings also highlight the importance of exploring multiple dimensions of the complex human mothering phenotype.

Cartilage repair of the ankle: first results of T2 mapping at 7.0 T after microfracture and matrix associated autologous cartilage transplantation.

BACKGROUND: Both microfracture (MFX) and matrix associated autologous cartilage transplantation (MACT) are currently used to treat cartilage defects of the talus. T2 mapping of the ankle at 7 T has the potential to assess the collagen fibril network organization of the native hyaline cartilage and of the repair tissue (RT). This study provides first results regarding the properties of cartilage RT after MFX (mean follow-up: 113.8 months) and MACT (65.4 months). METHODS: A multi-echo spin-echo sequence was used at 7 T to assess T2 maps in 10 volunteer cases, and in 10 cases after MFX and MACT each. Proton weighted morphological images and clinical data were used to ensure comparable baseline criteria. RESULTS: A significant zonal variation of T2 was found in the volunteers. T2 of the superficial and the deep layer was 39.3 ± 5.9 ms and 21.1 ± 3.1 ms (zonal T2 index calculated by superficial T2/deep T2: 1.87 ± 0.2, P < 0.001). In MFX, T2 of the reference cartilage was 37.4 ± 5.0 ms and 25.3 ± 3.5 ms (1.51 ± 0.3, P < 0.001). In the RT, T2 was 43.4 ± 10.5 ms and 36.3 ± 7.7 ms (1.20 ± 0.2, P = 0.009). In MACT, T2 of the reference cartilage was 39.0 ± 9.1 ms and 27.1 ± 6.6 ms (1.45 ± 0.2, P < 0.001). In the RT, T2 was 44.6 ± 10.4 ms and 38.6 ± 7.3 ms (1.15 ± 0.1, P = 0.003). The zonal RT T2 variation differed significantly from the reference cartilage in both techniques (MFX: P = 0.004, MACT: P = 0.001). CONCLUSION: T2 mapping at 7 T allows for the quantitative assessment of the collagen network organization of the talus. MACT and MFX yielded RT with comparable T2 properties.

Assessment of articular cartilage repair tissue after matrix-associated autologous chondrocyte transplantation or the microfracture technique in the ankle joint using diffusion-weighted imaging at 3 Tesla.

OBJECTIVE: The objective was to compare patients after matrix-associated autologous chondrocyte transplantation (MACT) and microfracture therapy (MFX) of the talus using diffusion-weighted imaging (DWI), with morphological and clinical scoring. MATERIALS AND METHODS: Twenty patients treated with MACT or MFX (10 per group) were examined using 3 T magnetic resonance imaging (MRI) at 48 ± 21.5 and 59.6 ± 23 months after surgery, respectively. For comparability, patients from each group were matched by age, body mass index, and follow-up. American Orthopaedic Foot and Ankle Society (AOFAS) score served as clinical assessment tool pre- and postoperatively. DWI was obtained using a partially balanced, steady-state gradient echo pulse sequence, as well as the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, based on a 2D proton density-weighted turbo spin-echo sequence and a 3D isotropic true fast imaging with steady-state precession sequence. Semi-quantitative diffusion quotients were calculated after region of interest analysis of repair tissue (RT) and healthy control cartilage, and compared among both groups. RESULTS: The mean AOFAS score improved significantly (P = 0.001) for both groups (MACT: 48.8 ± 20.4-83.6 ± 9.7; MFX: 44.3 ± 16.5-77.6 ± 13.2). No differences in the AOFAS (P = 0.327) and MOCART (P = 0.720) score were observed between MACT and MFX postoperatively. DWI distinguished between healthy cartilage and cartilage RT in the MFX group (P = 0.016), but not after MACT treatment (P = 0.105). Significant correlations were found between MOCART score and DWI index after MFX (Pearson: -0.648; P = 0.043), and between the diffusivity and longer follow-up interval in MACT group (Pearson: -0.647, P = 0.043). CONCLUSION: Whereas conventional scores reveal a similar outcome after MACT or MFX treatment in the ankle joint, DWI was able to distinguish between different RT qualities, as reported histologically for these diverse surgical procedures.

The European Psychiatric Association (EPA) guidance on suicide treatment and prevention.

UNLABELLED: Suicide is a major public health problem in the WHO European Region accounting for over 150,000 deaths per year. SUICIDAL CRISIS: Acute intervention should start immediately in order to keep the patient alive. DIAGNOSIS: An underlying psychiatric disorder is present in up to 90% of people who completed suicide. Comorbidity with depression, anxiety, substance abuse and personality disorders is high. In order to achieve successful prevention of suicidality, adequate diagnostic procedures and appropriate treatment for the underlying disorder are essential. TREATMENT: Existing evidence supports the efficacy of pharmacological treatment and cognitive behavioural therapy (CBT) in preventing suicidal behaviour. Some other psychological treatments are promising, but the supporting evidence is currently insufficient. Studies show that antidepressant treatment decreases the risk for suicidality among depressed patients. However, the risk of suicidal behaviour in depressed patients treated with antidepressants exists during the first 10-14 days of treatment, which requires careful monitoring. Short-term supplementary medication with anxiolytics and hypnotics in the case of anxiety and insomnia is recommended. Treatment with antidepressants of children and adolescents should only be given under supervision of a specialist. Long-term treatment with lithium has been shown to be effective in preventing both suicide and attempted suicide in patients with unipolar and bipolar depression. Treatment with clozapine is effective in reducing suicidal behaviour in patients with schizophrenia. Other atypical antipsychotics are promising but more evidence is required. TREATMENT TEAM: Multidisciplinary treatment teams including psychiatrist and other professionals such as psychologist, social worker, and occupational therapist are always preferable, as integration of pharmacological, psychological and social rehabilitation is recommended especially for patients with chronic suicidality. FAMILY: The suicidal person independently of age should always be motivated to involve family in the treatment. SOCIAL SUPPORT: Psychosocial treatment and support is recommended, as the majority of suicidal patients have problems with relationships, work, school and lack functioning social networks. SAFETY: A secure home, public and hospital environment, without access to suicidal means is a necessary strategy in suicide prevention. Each treatment option, prescription of medication and discharge of the patient from hospital should be carefully evaluated against the involved risks. TRAINING OF PERSONNEL: Training of general practitioners (GPs) is effective in the prevention of suicide. It improves treatment of depression and anxiety, quality of the provided care and attitudes towards suicide. Continuous training including discussions about ethical and legal issues is necessary for psychiatrists and other mental health professionals.

Gene-environment interactions between CRHR1 variants and physical assault in suicide attempts.

Risk factors for suicidal behaviors are partly heritable, including genetic variants that drive diathesis-stress in addition to, or by interaction with, exposure to certain stressful life events (SLEs). Hypothalamic-pituitary-adrenal (HPA) axis regulatory genes are candidates for association with suicide as well as its endophenotypes. Using a family-based design of offspring who attempted suicide (SA) and both parents, we investigated gene-environment interactions (G×Es) of SLE exposures with single nucleotide polymorphisms (SNPs) in corticotropin-releasing hormone receptor-1 (CRHR1), a major HPA axis regulatory gene. We observed a novel G×E among predominantly female SA between 5'-SNP rs7209436 and childhood/adolescence physical assault or attack (PA), as well as a second novel and male-specific G×E between 3'-SNP rs16940665 and adulthood PA exposure. A third male-specific G×E previously reported by us among depressed SA, between SNP rs4792887 and cumulative SLEs, was also further confirmed. The two novel G×Es presented here shared the SA characteristic of aggression, while showing differences on other aspects of SA heterogeneity. We conclude that different SA subjects were observed to differentially associate with two novel G×Es involving exposures to PA with different life timing and SNPs located in opposite ends of CRHR1. Concerning sex differences, we observed three subsets of distinct male SA that associated with each of the three observed G×Es, whereas female SAs were affected by only one of the G×Es. These results are consistent with a diathesis-stress model of suicidal behavior and may help to explain SA heterogeneity.

Serotonin transporter allelic variation in mothers predicts maternal sensitivity, behavior and attitudes toward 6-month-old infants.

Maternal behavior in the new mother is a multidimensional set of responses to infant cues that are influenced by the mother's early life experiences. In this study, we wanted to test if mothers' early life experiences and mothers' genotype have interactive effects on maternal behaviors and attitudes, something which has not been previously explored. In a sample of 204 mothers, we assessed maternal genotype at the serotonin transporter-linked polymorphic region (5-HTTLPR) and an adjacent upstream polymorphism (rs25531), together giving rise to three alleles: short (S), L(G) and L(A). Controlling for maternal age and parity, we showed that this genotype can predict differences in maternal sensitivity at 6 months postpartum: mothers with an S (or the functionally similar L(G)) allele were more sensitive than mothers who lacked the allele during a 30-min recorded mother-infant interaction (F (4,140) = 3.43; P = 0.01). Furthermore, we found highly significant gene-environment interactions in association with maternal behavior, such that mothers with no S or L(G) alleles oriented away more frequently from their babies if they also reported more negative early care quality (F (5,138) = 3.28; P = 0.008). Finally, we found significant gene-environment associations with maternal attitudes; mothers with the S allele and with greater early care quality scored higher on ratings of their perceived attachment to their baby (F (5,125) = 3.27; P = 0.008). The regression results show significant interactions between the reported quality of care mothers received from their own parents and genotype on both their frequency of orienting away from the infant during the interaction (F(5, 138) = 3.28; P = 0.008, Fig. 1a) and their perceived attachment feelings to the infant (F(5, 125) = 3.27; P = 0.008, Fig. 1b); however the direction of the effects for these two outcome measures were different from one another. With increasing care quality, mothers with the L(A)L(A) genotype (no S or L(G) allele) oriented away less frequently, while S or L(G) allele carriers showed no significant change. In contrast, with increasing early care quality. L(A)L(A) (no S or L(G) allele) mothers scored lower on perceived attachment to their infants, whereas S or L(G) allele carrying mothers scored higher. [corrected].